摘要
目的探讨吸烟和CYP2C19功能缺失性等位基因交互作用对氯吡格雷抗血小板反应性的影响。方法该研究连续募集2011年9月—2013年9月解放军总医院住院并接受阿司匹林和氯吡格雷双联抗血小板治疗的急性冠脉综合征(ACS)患者。采用光密度比浊法(LTA)测定氯吡格雷治疗前后的血小板聚集率,SnaPshot法检测CYP2C19功能缺失性等位基因变异型。利用单因素和多因素统计方法,分析吸烟和CYP2C19基因型交互作用对氯吡格雷治疗前后的血小板聚集率和治疗期间高血小板反应性(HPR)的影响。结果该研究共纳入500例患者,吸烟组203例(40.6%),非吸烟组297例(59.4%)。在非吸烟组,氯吡格雷治疗后的稳定血小板聚集率在CYP2C19*2携带者(*1/*2:43.24±19.39;*2/*2:53.52±19.88)和非携带者(*1/*1:37.91±19.12)之间差异均有统计学意义(校对后P值分别为P=0.029,P<0.001);而在吸烟组中未见上述差异。非吸烟组中至少一个CYP2C19*2等位基因携带者与非携带者之间的HPR的发生率差异有统计学意义(校正后OR:2.13,95%CI:1.23-3.72,P=0.008),而在吸烟组中未见上述差异(校正后OR:1.41;95%CI:0.65-3.04,P=0.387)。结论吸烟和CYP2C19功能缺失性等位基因的交互作用能够影响ACS患者中氯吡格雷的抗血小板反应性。
Objective To investigate the interaction of smoking status and CYP2C19 lose-of-function alleles on platelet reactivity in acute coronary syndrome（ACS）patients treated with clopidogrel.MethodsConsecutive ACS patients on aspirin and clopidogrel dual antiplatelet therapy were enrolled from September1 st,2011 to September 1st,2013 from Chinese PLA General Hospital.ADP-induced platelet aggregation was measured by light transmission aggregation（LTA）before clopidogrel administration and after 5 days maintenance dose of clopidogrel.SnaPshot method was applied to detect CYP2C19 loss-of-function alleles.The interaction between smoking status and CYP2C19 alleles of platelet aggregation before and after clopidogrel therapy,as well as high on-treatment platelet reactivity（HTPR）were analyzed by univariate analysis and multivariate analysis.Results A total of 500 ACS patients on maintenance aspirin and clopidogrel therapy were enrolled,including 203 smokers（40.6%）and 297 nonsmokers（59.4%）.In nonsmokers,a significant difference between CYP2C19＊2 carriers（＊1/＊2：43.24±19.39;＊2/＊2：53.52±19.88）and non-carriers（＊1/＊1：37.91±19.12）of clopidogrel platelet aggregation（adjusted P=0.029,P〈0.001,respectively）could be observed,but no significance in smokers.In addition,clopidogrel on-treatment platelet reactivity was significantly different between CYP2C19＊2 carriers and non-carriers（adjusted OR：2.13,95%CI：1.23-3.72,P=0.008）in non-smokers however,we didn＇t find the significance between CYP2C19＊2 carriers and non-carriers（adjusted OR：1.41;95%CI：0.65-3.04,P=0.387）in smokers.Conclusion This study indicates that the interaction of smoking status and CYP2C19 lose-of-function alleles can effect platelet reactivity in ACS patients treated with clopidogrel.
出处
《中国煤炭工业医学杂志》
2014年第11期1721-1725,共5页
Chinese Journal of Coal Industry Medicine
基金
国家自然科学基金面上项目(30971259
30570736
81100215/C03030201)
解放军总医院临床扶持基金(No.2012FC-TSYS-3043)
